Patients suffering from chronic pancreatitis are often considered for total or near-total pancreatectomy to ameliorate their chronic pain and dependence on narcotic agents. Total pancreatectomy, however, leads to diabetes mellitus and complications. However, advances in the techniques of isolating and purifying pancreatic islets from pancreata have made auto-islet transplantation feasible. Auto-islet transplantation will prevent the development of post-pancreatectomy diabetes and the secondary complications. Pancreatic islets when injected into the portal vein embolize to the liver and eventually re-vascularize. They possibly also re- innervate and have an altered pattern of hormonal secretion. Because allogeneic pancreatic islet transplants have not been uniformly successful, there are few metabolic studies with only limited data. Therefore, we propose to perform 20 auto-islet transplants over a period of 2 years. Seven patients will be studied approximatly 12 months post-pancreatectomy who have received total pancreatectomy without islet transplantation. Isolated islets will be injected into the liver via the portal vein after completion of the pancreatectomy. We will examine (i) the feasibility of total or near-total pancreatectomy followed by auto- islet transplantation on relief of pain, psychological and psychosocial functioning, and narcotic use and (ii) islet function and glucose metabolism. At the Indiana University Medical Center, we have established the infrastructure and experience necessary for isolating, purifying, and testing of human pancreatic islets. As part of our clinical human pancreatic islet transplant program, we have performed 9 allogeneic and 1 auto-islet transplants. The patient who received near-total pancreatectomy and auto-islet transplantation has been free of pain and is insulin independent (4 months). There has been no mortality associated with the procedure.